Prostate cancer (CaP) is the commonest internal malignancy in U.S. males, accounting for 192,000 new cases and 27,300 deaths annually. However, CaP also exists in a common, non-fatal, insignificant form which does not cause disease. Up to half of newly diagnosed CaP cases qualify histologically as insignificant, but 90% of men with CaP, serious and not, choose immediate curative therapy. Ability to image cancer within the prostate would help define the important cancers, but presently that ability is lacking. We propose to evaluate an advanced imaging system, the Artemis device, in men undergoing prostate biopsy to exclude malignancy. The device employs digital video processing of conventional ultrasound images to (1) create a contemporaneous 3D reconstruction of the prostate, (2) plan biopsy sites systematically, (3) digitally record the biopsy sites for future re-call, and (4) fuse or superimpose previously-obtained magnetic-resonance imaging (MRI) of the prostate with concurrent ultrasound images in a real-time manner. Potential advantages of this new technology include improved ability to sample the entire prostate thoroughly, to precisely record sampling sites for future re-biopsy, and to directly use images from MRI as well as ultrasound for biopsy targeting. MRI of the prostate, when performed in a multi-modal fashion---3Tesla coil combined with dynamic contrast enhancement and diffusion-weighted imaging---appears to be approaching clinical utility in visualizing cancer within the prostate. In the present study, results obtained with the new imaging system would be compared with (1) findings on whole-mount prostate pathology, for men undergoing prostatectomy (N=350/yr at UCLA), and (2) biopsy findings at diagnosis and subsequently, for men undergoing active surveillance (vast unmet need in Southern California). Accuracy of ultrasound/MRI fusion would be tested by comparing location of fiducial markers in the prostate seen on each of the two modalities. Value of MRI as a biopsy guide would be tested by comparing results of biopsies targeted at suspicious lesions seen on MRI vs 12-core systematic biopsies. The surveillance arm will provide opportunity for longitudinal testing of the imaging device in men with low- risk CaP in a structured, prospective program. Improved imaging and precise biopsy of the prostate, as provided by multi-modal MRI and the Artemis device, may help re-define significant and insignificant cancer.